Multi-Omics Analysis,Dataset Construction,and Validation Study Of Key Regulatory Molecules And Networks Involved In Mesenchymal-to-Epithelial Transition During Kidney Development

The Mesenchymal to Epithelial Transition(MET),in which metanephric mesenchymal cells transform into epithelial cells during kidney development,is a crucial step in kidney formation and provides the necessary foundation for its normal function.As an important process in organism development,its regulatory mechanism needs further clarification.The development of transcriptomics and epigenomics provides us with comprehensive biological information,enabling more comprehensive and in-depth exploration of the regulatory mechanisms of biological processes.Based on metanephric mesenchymal cell m K3 and epithelial-like cell m K4,we used transcriptome sequencing,quantitative proteomics,ATAC-seq and Ch IP-seq,combined with algorithms such as Net Act,RGT-HINT and Rcis Target to explore key signaling pathways and transcriptional regulators that involved in mesenchymal-epithelial transition during embryonic kidney development from three aspects: chromatin accessibility,histone methylation and gene expression.Integrated analysis was also used to find correlation among chromatin accessibility,histone methylation,transcription factor and gene expression.Multiple differentially expressed genes and proteins,differentially open chromatin regions and differentially methylated histone regions were identified during the mesenchymal-to-epithelial transition process.We have screened out multiple signaling pathways and transcription factors that regulate mesenchymal-to-epithelial transition and constructed a transcription factor regulatory network and a non-coding RNA-mediated competing endogenous RNA(ce RNA)regulatory network.In addition,there was a strong correlation among chromatin accessibility,H3K4me3 histone methylation,transcription factor binding and gene expression,indicating their co-regulation effect on mesenchymal and epithelial transcriptomes.We constructed mesenchymal-to-epithelial transition-related datasets based on the above data and verified it through external data,which showed good credibility and applicability of our genesets.Based on transcriptomics,chromatin accessibility and histone modification,our study provides a molecular regulatory network of cell mesenchymal-to-epithelial transition during embryonic kidney development.It provides a large amount of original data for researchers in related fields and offers new clues and ideas for related research.